title: The HsRAD51B-HsRAD51C stabilizes the HsRAD51 nucleoprotein filament.
abstract: There are six human RAD51 related proteins (HsRAD51 paralogs), HsRAD51B, HsRAD51C, HsRAD51D, HsXRCC2, HsXRCC3 and HsDMC1, that appear to enhance HsRAD51 mediated homologous recombinational (HR) repair of DNA double strand breaks (DSBs). Here we model the structures of HsRAD51, HsRAD51B and HsRAD51C and show similar domain orientations within a hypothetical nucleoprotein filament (NPF). We then demonstrate that HsRAD51B-HsRAD51C heterodimer forms stable complex on ssDNA and partially stabilizes the HsRAD51 NPF against the anti-recombinogenic activity of BLM. Moreover, HsRAD51B-HsRAD51C stimulates HsRAD51 mediated D-loop formation in the presence of RPA. However, HsRAD51B-HsRAD51C does not facilitate HsRAD51 nucleation on a RPA coated ssDNA. These results suggest that the HsRAD51B-HsRAD51C complex plays a role in stabilizing the HsRAD51 NPF during the presynaptic phase of HR, which appears downstream of BRCA2-mediated HsRAD51 NPF formation.
authors.affiliation: Department of Molecular Virology, Immunology, and Medical Genetics, Human Cancer Genetics, The Ohio State University Medical Center and Comprehensive Cancer Center, OH 43210, USA.
authors.forename: Ravindra
authors.initials: R
authors.lastname: Amunugama
authors.forename: Joanna
authors.initials: J
authors.lastname: Groden
authors.forename: Richard
authors.initials: R
authors.lastname: Fishel
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry; D000818:Animals; D004277:DNA, Single-Stranded / Q000737:chemistry*; D004278:DNA, Superhelical / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry*; D059765:Homologous Recombination; D006801:Humans; D008958:Models, Molecular; D009698:Nucleoproteins / Q000737:chemistry; D011485:Protein Binding; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D051135:Rad51 Recombinase / Q000737:chemistry*; D053484:RecQ Helicases / Q000737:chemistry; D051716:Replication Protein A / Q000737:chemistry; D061987:Sf9 Cells; D018411:Spodoptera; D040681:Structural Homology, Protein
chemical_list: D004277:DNA, Single-Stranded; D004278:DNA, Superhelical; D004268:DNA-Binding Proteins; D009698:Nucleoproteins; C413002:RAD51B protein, human; C448305:RAD51C protein, human; D051716:Replication Protein A; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D053484:RecQ Helicases
keywords: ATPase, Bloom's syndrome; BLM; Homologous recombination; RAD51 paralogs